Epilepsy is one of the oldest diseases in the world. According to reports of the World Health Organization, the number of patients worldwide is up to 50 million, and there are 6000 new cases every day. The epidemiological data of China shows that, in China, the total prevalence rate of epilepsy is 7 ‰, the annual incidence rate is 28.8 per 100 thousand, the prevalence rate of “active epilepsy” is 4.6 ‰, and the prevalence rate of active epilepsy, the seizure of which has been occurred within 2 and 5 years, is 4.9 ‰ and 5.4 ‰, respectively. Accordingly, it is estimated that there are about 9 million epilepsy patients in China, wherein about 4 million patients fail to receive normal treatment, and there are about 400 thousands new epilepsy patients in China every year. Therefore, the health administrators, medical and scientific researchers, and social workers in China are facing great challenges in the field of epilepsy.
Pregabalin, an agonist of the GABA receptor developed by Pfizer, was approved in June 2005 for adjuvant therapy for local seizure epilepsy of adults, which is the most promising one of the developed drugs for treating epilepsy. Compared with gabapentin, pregabalin has stronger anti-convulsive effect, fewer side effects, less dosage, fewer taking times, and also has anti-anxiety effect and other advantages. Moreover, it has no interaction with the existing antiepileptic drugs, thus it is easy to combine with other antiepileptic drugs for synergistic treatment of epilepsy. Meanwhile, this product is also a therapeutic drug for diabetic peripheral neuropathy-related neuralgia, herpes zoster neuralgia, fibromyalgia and alike. It is used in a wide range of people, and has broad market prospect. This drug is considered as a blockbuster drug once marketed. Some analysts predicted that the market would reach 10 billion US dollars by 2016.
Currently, there are two main types of methods reported for preparing pregabalin intermediate 3-carbamoymethyl-5-methylhexanoic acid. One is to obtain 3-carbamoymethyl-5-methylhexanoic acid by ammonolysis of 3-isobutylglutaric anhydride (Compound 1) in the presence of certain organic solvents and under the condition of ammonia water. The other is to obtain 3-carbamoymethyl-5-methylhexanoic acid by racemic recovery of the mother liquor after resolution.

However, the methods of the first type reported currently in literatures are adding certain organic solvents as reaction medium, wherein the most common solvent is methyl tert-butyl ether (see for example, PCT International Application WO2012093411 A2 filed by Dr. Braja Sundar Pradhan in 2012). It is also reported in several domestic literatures, but methyl tert-butyl ether is added into each of the systems for preparing 3-carbamoymethyl-5-methylhexanoic acid as a solvent.